Target Information
| Target General Information | Top | |||||
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| Target ID |
T20600
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| Target Name |
Caspase-6 (CASP6)
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| Synonyms |
MCH2; Caspase-6 subunit p18; Caspase-6 subunit p11; CASP-6; Apoptotic protease Mch-2
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| Gene Name |
CASP6
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death. Involved in the activation cascade of caspases responsible for apoptosis execution.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.22.59
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| Sequence |
MSSASGLRRGHPAGGEENMTETDAFYKREMFDPAEKYKMDHRRRGIALIFNHERFFWHLT
LPERRGTCADRDNLTRRFSDLGFEVKCFNDLKAEELLLKIHEVSTVSHADADCFVCVFLS HGEGNHIYAYDAKIEIQTLTGLFKGDKCHSLVGKPKIFIIQACRGNQHDVPVIPLDVVDN QTEKLDTNITEVDAASVYTLPAGADFLMCYSVAEGYYSHRETVNGSWYIQDLCEMLGKYG SSLEFTELLTLVNRKVSQRRVDFCKDPSAIGKKQVPCFASMLTKKLHFFPKSN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A05675 | |||||
| HIT2.0 ID | T25NS3 | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 5-Fluoro-2-({[3-(Pyrimidin-2-Yl)pyridin-2-Yl]amino}methyl)phenol | Ligand Info | |||||
| Structure Description | Tailoring Small Molecules for an Allosteric Site on Procaspase-6 | PDB:4NBL | ||||
| Method | X-ray diffraction | Resolution | 1.76 Å | Mutation | Yes | [2] |
| PDB Sequence |
AFYKREMFDP
33 AEKYKMDHRR43 RGIALIFNHE53 RFFWHLTLPE63 RRGTCADRDN73 LTRRFSDLGF 83 EVKCFNDLKA93 EELLLKIHEV103 STVSHADADC113 FVCVFLSHGE123 GNHIYAYDAK 133 IEIQTLTGLF143 KGDKCHSLVG153 KPKIFIIQAA163 RGNQHDVPVI173 PDTNITEVDA 194 ASVYTLPAGA204 DFLMCYSVAE214 GYYSHRETVN224 GSWYIQDLCE234 MLGKYGSSLE 244 FTELLTLVNR254 KVSQRRVDFC264 KDPSAIGKKQ274 VPCFASMLTK284 KLHFFPKS |
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| Ligand Name: 2-{[(3-Methylpyridin-2-yl)amino]methyl}phenol | Ligand Info | |||||
| Structure Description | Tailoring Small Molecules for an Allosteric Site on Procaspase-6 | PDB:4NBK | ||||
| Method | X-ray diffraction | Resolution | 1.94 Å | Mutation | Yes | [2] |
| PDB Sequence |
FYKREMFDPA
34 EKYKMDHRRR44 GIALIFNHER54 FFWHLTLPER64 RGTCADRDNL74 TRRFSDLGFE 84 VKCFNDLKAE94 ELLLKIHEVS104 TVSHADADCF114 VCVFLSHGEG124 NHIYAYDAKI 134 EIQTLTGLFK144 GDKCHSLVGK154 PKIFIIQAAR164 GNQHDVPVIP174 TNITEVDAAS 196 VYTLPAGADF206 LMCYSVAEGY216 YSHRETVNGS226 WYIQDLCEML236 GKYGSSLEFT 246 ELLTLVNRKV256 SQRRVDFCKD266 PSAIGKKQVP276 CFASMLTKKL286 HFFPKS |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Apoptosis | hsa04210 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 3.17E-04 |
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| Closeness centrality | 2.40E-01 | Radiality | 1.42E+01 | Clustering coefficient | 2.22E-01 |
| Neighborhood connectivity | 5.67E+01 | Topological coefficient | 1.38E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Apoptosis | |||||
| References | Top | |||||
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| REF 1 | Caspase inhibitors: a review of recently patented compounds (2013-2015).Expert Opin Ther Pat. 2018 Jan;28(1):47-59. | |||||
| REF 2 | Tailoring small molecules for an allosteric site on procaspase-6. ChemMedChem. 2014 Jan;9(1):73-7, 2. | |||||
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